This invention relates to healing wounds.
Growth factors are polypeptide hormones which stimulate a defined population of target cells. Examples of growth factors include platelet-derived growth factor (PDGF), insulin-like growth factor, transforming growth factor beta (TGF-.beta.), transforming growth factor alpha, epidermal growth factor (EGF), and fibroblast growth factor. PDGF is a cationic, heat-stable protein found in the granules of circulating platelets which is known to stimulate in vitro protein synthesis and collagen production by fibroblasts. It is also known to act as an in vitro mitogen and chemotactic agent for fibroblasts, and smooth muscle cells.
It has been proposed to use PDGF to promote in vivo wound healing. For example, Grotendorst (1984) J. Trauma 24:549-52 describes adding PDGF to Hunt-Schilling wire mesh chambers impregnated with a collagen gel and implanted in the backs of rats; PDGF was found to increase the amount of new collagen synthesized. However, Leitzel et al. (1985) J. Dermatol. Surg. Oncol. 11:617-22 were unable to accelerate normal wound healing in hamsters using PDGF alone or in combination with FGF and EGF.
Michaeli, et al. (1984) In Soft and Hard Tissue Repair (Hunt, T.K. et al., Eds), Praeger Publishers, New York, pp. 380-394, report that application of a partially purified preparation of PDGF obtained from platelet-rich plasma stimulated angiogenesis when implanted in rabbit corneas. Because PDGF is not an angiogenic growth factor the investigators suggested that an unknown factor in their partially purified PDGF preparation was responsible for the angiogenic effect.
Lawrence et al. 203 Ann. Surgery 142, 1986 demonstrate a synergisic wound healing activity when TGF-.beta., PDGF and EGF are used together at 100 ng/ml each but not with PDGF in combination with EGF alone. Lynch et al. 84 Proc. Nat. Acad. Sci. USA 7696, 1987 state that a preparation containing equal amounts (5ng/mm.sup.2) of EGF and PDGF did not elicit wound healing activity greater than that brought about by EGF or PDGF alone.